22204-53-1Relevant articles and documents
Asymmetric Synthesis of (S)-2-(6-methoxy-2-naphthyl)propanoic Acid
Hiyama, Tamejiro,Saito, Kumi,Sato, Ken-ichi,Wakasa, Noriko,Inoue, Masuo
, p. 1471 - 1472 (1986)
For the synthesis of the title compound of 60 percent ee, a new method is established which involves cyanation of an acetal derived from 1-(6-methoxy-2-naphthyl)ethanone and (S,S)-2,4-pentanediol, alkaline hydrolysis, and finally hydrogenolysis with palladium catalyst.
Disposition of naproxen, naproxen acyl glucuronide and its rearrangement isomers in the isolated perfused rat liver
Lo,Addison,Hooper,Dickinson
, p. 309 - 319 (2001)
1. An isolated perfused rat liver (IPRL) preparation was used to investigate separately the disposition of the non-steroidal anti-inflammatory drug (NSAID) naproxen (NAP), its reactive acyl glucuronide metabolite (NAG) and a mixture of NAG rearrangement isomers (isoNAG), each at 30 μg NAP equivalents ml-1 perfusate (n = 4 each group). 2. Following administration to the IPRL, NAP was eliminated slowly in a log-linear manner with an apparent elimination half-life (t1/2) of 13.4 ± 4.4 h. No metabolites were detected in perfusate, while NAG was the only metabolite present in bile in measurable amounts (3.9 ± 0.8% of the dose). Following their administration to the IPRL, both NAG and isoNAG were rapidly hydrolysed (t1/2 in perfusate = 57 ± 3 and 75 ± 14 min respectively). NAG also rearranged to isoNAG in the perfusate. Both NAG and isoNAG were excreted intact in bile (24.6 and 14.8% of the NAG and isoNAG doses, respectively). 3. Covalent NAP-protein adducts in the liver increased as the dose changed from NAP to NAG to isoNAG (0.20 to 0.34 to 0.48% of the doses, respectively). Similarly, formation of covalent NAP-protein adducts in perfusate were greater in isoNAG-dosed perfusions. The comparative results suggest that isoNAG is a better substrate for adduct formation with liver proteins than NAG.
New synthesis of optically active α-arylpropanoic acid: The asymmetric hydrogenation of atropic acid over cinchona-modified Pd/Fe2O3 catalysts
Ma,Wang,Shi
, p. 175 - 182 (2003)
The first satisfactory application of the heterogeneous cinchona-modified Pd/Fe2O3 catalyst system in the synthesis of optically active α-arylpropanoic acid, namely, the highly enantioselective (up to 87% ee) hydrogenation of atropic acid to S-(+)-naproxen is described.
Fabrication of a nano-drug delivery system based on layered rare-earth hydroxides integrating drug-loading and fluorescence properties
Gu, Qingyang,Chen, Wen,Duan, Fei,Ju, Ruijun
, p. 12137 - 12143 (2016)
We demonstrate the first example of intercalation of naproxen (abbr. NPX) into layered europium hydroxide (LEuH) and investigate the structure, chemical composition, thermostability, morphology, luminescence properties, cytotoxic effect, and controlled-release behaviors. Different deprotonation degrees lead to NPX-LEuH composites with diverse structures (horizontal or vertical arrangement), and the thermal stability of organics is enhanced after intercalation. The Eu3+ luminescence in NPX-LEuH composites is enhanced, especially for the NPX-LEuH-1: 0.5 composite. The content of naproxen in the intercalation material can be confirmed by HPLC. The cytotoxic effect of LEuH is observed with a sulforhodamine B (SRB) colorimetric assay, which reveals that the LEuH has low cytotoxic effects on most cells. In addition, the NPX-LEuH nanocomposites can control the release of NPX in Na2HPO4-NaH2PO4 buffer solution at pH 6.86 and 37 °C, and the complete release needs about 200 min. The release mechanism can be ascribed to the ion-exchange reaction between NPX and HPO42-/H2PO4- in bulk solution. The ion-exchange velocity is fast at the beginning and slows down gradually with the exchange reaction. The construction of LRH composites with drug molecules provides a beneficial pathway for preparing a nano-drug delivery system based on LRHs integrating drug-loading and fluorescence properties.
Asymmetric dihydroxylation in an approach to the enantioselective synthesis of 2-arylpropanoic acid non-steroidal anti-inflammatory drugs
Griesbach, Robert C.,Hamon, David P. G.,Kennedy, Rebecca J.
, p. 507 - 510 (1997)
Naproxen ((S)-2-(6-methoxy-2-naphthyl)propanoic acid) and flurbiprofen ((S)2-3 -fluoro-4-phenylphenyl) propanoic acid) have been synthesised in high en antiomeric excess. The synthetic strategy employed waste introduce asymmetry into the molecules by Sharpless asymmetric dihydroxylation of the appropriate methyl styrenes. The resultant diols were then converted into optically active epoxides and the required stereogenic centre was assembled by catalytic hydrogenolysis of the introduced benzylic epoxide oxygen bond, followed by oxidation of the derived optically active primary alcohol.
Preparation of One-Pot Immobilized Lipase with Fe3O4 Nanoparticles Into Metal-Organic Framework For Enantioselective Hydrolysis of (R,S)-Naproxen Methyl Ester
Ozyilmaz, Elif,Ascioglu, Sebahat,Yilmaz, Mustafa
, p. 3687 - 3694 (2021)
Immobilization of enzyme to magnetic metal-organic frameworks (MOF) can preserve biological functionality in harsh environments to increase enzymes activity, stability, and improve reusability. The magnetic Fe3O4 nanoparticles were treated with calix[4]arene tetracarboxylic acid (Calix) and Candida rugosa lipase (CRL), and then encapsulated into the zeolitic imidazole framework-8 (Fe3O4@Calix-ZIF-8@CRL). The lipase activity data of Fe3O4@Calix-ZIF-8@CRL was 2.88 times higher than that of the Fe3O4@ZIF-8@CRL (without Calix). The catalytic properties of immobilized lipases were studied on the enantioselective hydrolysis of R/S-naproxen methyl ester. It was also observed that Fe3O4@Calix-ZIF-8@CRL has excellent enantioselectivity (E=371) compared to Fe3O4@ZIF-8@CRL (E=131). Furthermore, Fe3O4@Calix-ZIF-8@CRL was seen to still retain 30 % of the conversion rate after the fifth reuse. This work may also be useful for the pharmaceutical industry due to the increased reusability and stability of enzymes, the enantiomeric selectivity exhibited by MOF-enzyme biocomposites, and the significant differences in the biological activities of the enantiomers.
Scalable synthesis of a new enantiomerically pure π-extended rigid amino indanol
Rendina, Victor L.,Goetz, Samantha A.,Neitzel, Angelika E.,Kaplan, Hilan Z.,Kingsbury, Jason S.
, p. 15 - 18 (2012)
A convenient route to a benzo-fused amino indanol chiral controller is disclosed. The synthesis is based on a newly optimized entry to 3H-benz(e)indene that can be performed on decagram scale with no purification of intermediates. Subsequent oxidation, classical resolution, and Ritter steps give the target synthon in >98% ee. The resolution features (S)-naproxen as an inexpensive and highly crystalline resolving agent. Conversion of the amino alcohol to its bis(oxazolinyl)-propane is also reported. A solid state structure of the CuCl2-box complex shows preservation of the distorted square planar geometry found in the parent CuCl2(indanyl-box) despite greater steric crowding by the blocking groups.
Asymmetric synthesis of acids by the palladium-catalyzed hydrocarboxylation of olefins in the presence of (R)-(-)- or (S)-(+)-1,1′-binaphthyl-2,2′-diyl hydrogen phosphate
Alper, Howard,Hamel, Nathalie
, p. 2803 - 2804 (1990)
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Enantioselective synthesis of (S)-naproxen using immobilized lipase on chitosan beads
Gilani, Saeedeh L.,Najafpour, Ghasem D.,Heydarzadeh, Hamid D.,Moghadamnia, Aliakbar
, p. 304 - 314 (2017)
S-naproxen by enantioselective hydrolysis of racemic naproxen methyl ester was produced using immobilized lipase. The lipase enzyme was immobilized on chitosan beads, activated chitosan beads by glutaraldehyde, and Amberlite XAD7. In order to find an appropriate support for the hydrolysis reaction of racemic naproxen methyl ester, the conversion and enantioselectivity for all carriers were compared. In addition, effects of the volumetric ratio of two phases in different organic solvents, addition of cosolvent and surfactant, optimum pH and temperature, reusability, and inhibitory effect of methanol were investigated. The optimum volumetric ratio of two phases was defined as 3:2 of aqueous phase to organic phase. Various water miscible and water immiscible solvents were examined. Finally, isooctane was chosen as an organic solvent, while 2-ethoxyethanol was added as a cosolvent in the organic phase of the reaction mixture. The optimum reaction conditions were determined to be 35?°C, pH?7, and 24?h. Addition of Tween-80 in the organic phase increased the accessibility of immobilized enzyme to the reactant. The optimum organic phase compositions using a volumetric ratio of 2-ethoxyethanol, isooctane and Tween-80 were 3:7 and 0.1% (v/v/v), respectively. The best conversion and enantioselectivity of immobilized enzyme using chitosan beads activated by glutaraldehyde were 0.45 and 185, respectively.
Metal-based scaffolds of Schiff bases derived from naproxen: Synthesis, antibacterial activities, and molecular docking studies
Shaheen, Muhammad Ashraf,Feng, Shanshan,Anthony, Mehwish,Tahir, Muhammad Nawaz,Hassan, Mubashir,Seo, Sung-Yum,Ahmad, Saeed,Iqbal, Mudassir,Saleem, Muhammad,Lu, Changrui
, (2019)
We report here the synthesis, characterization, and antibacterial evaluation of transition metal complexes of Ni, Cu, Co, Mn, Zn, and Cd (6a–f), using a Schiff base ligand (5) derived from naproxen (an anti-inflammatory drug) and 5-bromosalicylaldehyde by a series of reactions. The ligand and the synthesized complexes were characterized by elemental analysis, UV-Visible, FTIR, and XRD techniques. The ligand 5 behaves as a bidentate donor and coordinates with metals in square planar or tetrahedral fashion. In order to evaluate its bioactivity profile, we screened the Schiff base ligand and its metal complexes (6a–f) against different species of bacteria and the complexes were found to exhibit significant antibacterial activity. The complexes showed more potency against Bacillus subtilis as compared to the other species. Moreover, we modeled these complexes’ binding affinity against COX1 protein using computational docking.
Improvement of catalytic activity of lipase in the presence of wide rim substituted calix[4]arene carboxylic acid-grafted magnetic nanoparticles
Akceylan, Ezgi,Sahin, Ozlem,Yilmaz, Mustafa
, p. 113 - 123 (2014)
Candida rugosa lipase immobilized on calix[4]arene carboxylic acid-grafted magnetic nanoparticles using a sol-gel encapsulation technique was tested for activity, which was assessed both in the enantioselective hydrolysis of racemic Naproxen methyl ester and that of p-nitrophenylpalmitate. It has also been noticed that, compared to the free enzyme (E = 137) with an ee value of [98 %, S-Naproxen calix[4]arene carboxylic acid-grafted magnetic nanoparticles based on encapsulated lipase (Calix-1-MN and Calix-2-MN) offer excellent enantioselectivity (E = 373 and E = 381). Moreover, the results indicated that after the fifth reuse in the enantioselective reaction, the encapsulated lipase (Calix-2-MN) still retained about 43 % of its conversion power. Springer Science+Business Media Dordrecht 2013.
Highly effective soluble polymer-supported catalysts for asymmetric hydrogenation [2]
Fan, Qing-Hua,Ren, Chang-Yu,Yeung, Chi-Hung,Hu, Wen-Hao,Chan, Albert S. C.
, p. 7407 - 7408 (1999)
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Asymmetric transformation of the second kind of racemic naproxen
Lopez, Francisco J.,Ferrino, Sergio A.,Reyes, Mario S.,Roman, Ruth
, p. 2497 - 2500 (1997)
Several chiral derivatives of racemic naproxen were subjected to asymmetric transformations. Notably, asymmetric transformation of the second kind of a mixture of 2b and 3b gave a diastereomeric excess (d.e.) over 90% in favor of 2b. This d.e. was increased to over 99% after recrystallization.
Reactive immunization strategy generates antibodies with high catalytic proficiencies
Lo,Wentworth P.,Jung,Yoon,Ashley,Janda
, p. 10251 - 10252 (1997)
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Synthesis of diastereomeric anhydrides of (RS)-ketorolac and (RS)-etodolac, semi-preparative HPLC enantioseparation, establishment of molecular asymmetry and recovery of pure enantiomers
Malik, Poonam,Bhushan, Ravi
, p. 13681 - 13691 (2017)
Herein, enantioseparation of two anti-inflammatory drugs, namely, (RS)-ketorolac and (RS)-etodolac, commonly marketed and administered as racemates, was achieved by RP-HPLC. This method provided very low limit of detection values (3.69 and 3.02 ng mL-1 for diastereomeric derivatives of (R)- and (S)-Ket, respectively) as compared to those reported in literature. (S)-Naproxen benzotriazole ester, which was used as a chiral reagent, was synthesized and characterized by UV, IR, and 1H NMR spectroscopies, elemental analysis, and polarimetry. The diastereomeric derivatives were synthesized via microwave irradiation, separated on an analytical scale by RP-HPLC, and then isolated by preparative HPLC. The use of a mobile phase containing methanol and aqueous triethylamine phosphate (TEAP) in the isocratic mode was found to be successful for the separation of diastereomeric derivatives, and the separation conditions with respect to pH, flow rate, and buffer concentration were optimized. The diastereomeric derivatives were characterized, and their absolute configuration was established. Hydrolysis of the derivatives provided native enantiomers under mild reaction conditions. This study describes the successful enantioseparation of the above mentioned two analytes by semi-preparative HPLC with easy recovery of the native enantiomers without racemization and with the establishment of molecular asymmetry.
In vitro regioselective stability of β-1-O- and 2-O-acyl glucuronides of naproxen and their covalent binding to human serum albumin
Iwaki, Masahiro,Ogiso, Taro,Inagawa, Shinako,Kakehi, Kazuaki
, p. 52 - 57 (1999)
β-1-O- (NAG) and 2-O-glucuronides (2-isomer) of (S)-naproxen (NA) were prepared to determine which positional isomer(s) of the acyl glucuronide of NA is responsible for forming covalent adducts with human serum albumin (HSA). Their comparative stability and covalent binding adduct formation with HSA were investigated at pH 7.4 and at 37 °C. NA and its acyl glucuronides were simultaneously determined by HPLC. Three positional isomers were formed successively after incubation of NAG in the buffer only. However, when NAG was incubated with HSA (30 mg/mL), isomers other than the 2-isomer were formed in little or negligible quantities. In HSA solution, NAG (k(d) = 2.08 ± 0.08 h-1) was four times less stable than 2-isomer (k(d) 0.51 ± 0.02 h-1). NAG was degraded by hydrolysis (k(hyd) = 1.01 ± 0.10 h-1) and isomerization (k(iso) 1.07 ± 0.07 h-1) to the same extent; however, hydrolysis was predominant for the 2-isomer (k(d) = 0.51 ± 0.02 h-1). The incubation of both NAG and 2-isomer with HSA led to the formation of a covalent adduct; however, the adduct formation from the 2-isomer proceeded more slowly than that from NAG. The present results suggest that the covalent binding of NA to HSA via its acyl glucuronides proceeds through both transacylation (direct nucleophilic displacement) and glycation mechanisms; NAG rapidly forms an adduct that may be unstable, and the protein adduct from the 2-O-acyl glucuronide is as important for the covalent binding as those from the 1-O-acyl glucuronides.
Asymmetric Synthesis of Naproxen by a New Heterogeneous Catalyst
Wan, Kam T.,Davis, Mark E.
, p. 25 - 30 (1995)
A new heterogeneous, asymmetric catalyst is described.The catalyst is a modified version of the supported aqueous-phase catalyst reported previously (Wan and Davis, J.Catal. 148,1(1994)); ethylene glycol is used in place of water as the hydrophilic phase.Both the enantioselectivity and the activity of this new heterogeneous catalyst are comparable to the homogeneous analogue in neat methanol (or ethylene glycol); e.e.'s are 95.7percent vs 96.1percent and t.o.f.'s are 40.7 hr-1 vs 131.0 hr-1, respectively.Recycling of the catalyst is possible without leaching of ruthenium at a detection limit of 32 ppb.
Design and synthesis of Janus-type chiral dendritic diphosphanes and their applications in asymmetric hydrogenation
Liu, Ji,Feng, Yu,Ma, Baode,He, Yan-Mei,Fan, Qing-Hua
, p. 6737 - 6744 (2012)
A series of chiral diphosphane-functionalized Janus dendrimers (up to 16 BINAP units) have been readily synthesized by using liquid-phase organic synthesis with the third-generation Frechet-type poly(aryl ether) dendron as the soluble support. The resulting dendritic ligands were purified by simple solvent precipitation without the need for chromatographic separation at the end of reaction. Complete functionalization of the dendrimers with BINAP moieties was confirmed by 1H NMR, MALDI-TOF mass spectroscopy, and elemental analyses. Their ruthenium complexes were applied to the asymmetric hydrogenation of 2-arylacrylic acids. It was found that only slightly lower enantioselectivities were achieved than the corresponding small-molecular Ru catalyst. Interestingly, a clear increase in activity of the dendritic catalysts was observed on going to the higher generations. In addition, the third-generation catalyst could be recycled without significant loss of catalytic activity or enantioselectivity before the fifth catalytic run. A new kind of easily available Janus dendritic diphosphane ligand has been synthesized and their metal complexes were applied to the asymmetric hydrogenation of 2-arylacrylic acids. Interestingly, a clear increase in activity of the dendritic catalysts was observed on going to the higher generations. Furthermore, the third-generation catalyst could be recycled at least five times. Copyright
An Investigation of the Palladium-Catalyzed, Formate-Mediated Hydroxycarbonylation of optically active 1-Arylethyl Esters
Baird, Jeff M.,Kern, John R.,Lee, Gary R.,Morgans, David J.,Sparacino, Mark, L.
, p. 1928 - 1933 (1991)
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Synthesis, comparative docking, and pharmacological activity of naproxen amino acid derivatives as possible anti-inflammatory and analgesic agents
Elhenawy, Ahmed A.,Al-Harbi,Moustafa, Gaber O.,El-Gazzar,Abdel-Rahman, Rehab F.,Salim, Abd Elhamid
, p. 1773 - 1790 (2019)
Background and aim: Naproxen is a member of the Nonsteroidal anti-inflammatory drugs (NSAIDs). This work aimed to synthesize a safe NSAID agent based on a peptide derivative. Methods: The structure of compounds 5–20 was established on the basis of spectral data. Frontier molecular orbitals and chemical reactivity were discussed to clarify inter-and intramolecular interactions among tested compounds. We applied competitive molecular docking using polynomial logarithms to identify the most accurate algorithm for pharmacological activity prediction for the tested compounds. The docking protocol with the lowest RMSD was selected for analyzing binding affinity. Results: Docking results illustrated that the binding interaction increased after introduction of an acidic fragment to the parent compound. These compounds were selected for additional study against adsorption, distribution, metabolism, excretion, and toxicity (ADMET) in silico. The compounds tested had good oral bioavailability without any carcinogenesis effect; no marked health effects were observed via rodent toxicity. Compounds passed through docking and ADMET profiles for them (5–16) were examined as anti-inflammatory and analgesic agents. Compounds 8 and 16 showed higher anti-inflammatory potency than the reference drug and tested compounds. Compounds 8, 10, and 14 exhibited the highest analgesic potency compared to the other tested compounds. Conclusion: The tested compounds have shown negligible ulcerogenic effects, and may be considered safer drugs than naproxen for treating inflammatory conditions.
Asymmetric hydrogenation of 2-arylacrylic acids catalyzed by immobilized Rn-BINAP complex in 1-n-butyl-3-methylimidazolium tetrafluoroborate molten salt
Monteiro, Adriano L.,Zinn, Fabiano K.,De Souza, Roberto F.,Dupont, Jairton
, p. 177 - 179 (1997)
The [RuCl2-(S)-BINAP]2.NEt3 catalyst precursor dissolved in 1-n-butyl-3-methylimidazolium tetrafluoroborate molten salt is able-to hydrogenate 2-arylacrylic acids (aryl=Ph or 6-MeO-naphthyl) with enantioselectivities similar or higher than those obtained in homogeneous media. Moreover, the hydrogenated products can be quantitatively separated from the reaction mixture and the recovered ionic liquid catalyst solution can be reused several times without any significant changes in the catalytic activity or selectivity.
Reshaping the active pocket of esterase Est816 for resolution of economically important racemates
Fan, Xinjiong,Fu, Yao,Liu, Xiaolong,Zhao, Meng
, p. 6126 - 6133 (2021/09/28)
Bacterial esterases are potential biocatalysts for the production of optically pure compounds. However, the substrate promiscuity and chiral selectivity of esterases usually have a negative correlation, which limits their commercial value. Herein, an efficient and versatile esterase (Est816) was identified as a promising catalyst for the hydrolysis of a wide range of economically important substrates with low enantioselectivity. We rationally designed several variants with up to 11-fold increased catalytic efficiency towards ethyl 2-arylpropionates, mostly retaining the initial substrate scope and enantioselectivity. These variants provided a dramatic increase in efficiency for biocatalytic applications. Based on the best variant Est816-M1, several variants with higher or inverted enantioselectivity were designed through careful analysis of the structural information and molecular docking. Two stereoselectively complementary mutants, Est816-M3 and Est816-M4, successfully overcame and even reversed the low enantioselectivity, and several 2-arylpropionic acid derivatives with highEvalues were obtained. Our results offer potential industrial biocatalysts for the preparation of structurally diverse chiral carboxylic acids and further lay the foundation for improving the catalytic efficiency and enantioselectivity of esterases.
PHOTOLYTIC COMPOUNDS AND TRIPLET-TRIPLET ANNIHILATION MEDIATED PHOTOLYSIS
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Paragraph 0026, (2021/04/17)
The invention provides novel photolytic compounds and prodrugs, nanoparticles and compositions thereof, and methods of conducting photolysis mediated by triplet-triplet annihilation.
